Myc is an important regulator of many cellular processes, including growth promotion, differentiation, and apoptosis. The mechanisms underlying Myc biological activity, however, remain elusive. For many years, research in the field has focused on the idea of Myc as a transactivator of gene expression. More recently, alternative mechanisms of Myc function have been proposed, including gene repression. In this review we present several lines of evidence to support a connection between Myc-mediated transformation and transcriptional repression.